The intent of this proposed work is to use a recently developed model of rodent obesity, which produces ex-obese rats that appear to be similar to ex-obese humans, to study the changes in energy balance that occur during development and treatment of dietary obesity. Dietary obesity in humans develops slowly, with body fat gradually increasing over a period of years. It is difficult to perform studies in man that are sufficiently long to study the temporal changes in energy balance that occur during development of obesity. In obese humans, it is also unclear why it is so difficult to maintain a weight reduction once it has been achieved. In the model of rodent obesity, 6-7 months of high fat diet (HFD) feeding is associated with obesity that persists, even after dietary fat is reduced. This "persistent" obesity has been shown to be associated with a reduction in the amount of energy required to maintain body weight, with a preservation of body weight and body energy during food restriction, and with an abnormally high food efficiency during refeeding following food restriction. In these respects, ex-obese rats showing "persistent" obesity appear to be similar to ex-obese humans. A novel aspect of this project is that 24-hr energy expenditure will be determined weekly in rats during development and treatment of dietary obesity and will be used in conjunction with measures of all other components of energy balance to determine the fate of all ingested energy. A secondary goal of this work is to test the hypothesis that a reduction in insulin sensitivity develops with obesity and gives rise to a reduction in energy expenditure. Thus, treatments such as exercise, that are particularly effective in improving insulin sensitivity, may be necessary for successful treatment of persistent dietary obesity. The proposed work involves the study of both the development of dietary obesity and its treatment. Pertaining to development of obesity, studies are planned: to determine the time course during which persistent obesity develops; to determine if the persistent obesity occurs after development of a critical level of adiposity; and to determine if the type of fat in a high fat diet affects the nature of the resulting obesity. Pertaining to the treatment of obesity, studies are planned to: determine the effectiveness of exercise (with or without food restriction) in treating obesity; to determine the role of meal patterning in treatment of obesity; to determine the role of sustained weight reduction in lowering the level of body weight which the rats defend; and to determine the effects of weight cycling in weight reduction. In summary, this work involves the use of current energy balance measurement techniques to focus on 1) understanding the nature of the changes in energy balance that occur with dietary obesity and cause the obesity to be resistant to treatment; 2) determining how food restriction, exercise, meal patterning, and weight cycling can best be manipulated in successful treatment of persistent dietary obesity. Results of this work should have direct application to our understanding of how obesity develops and how it can be treated.